Role of BAX inthe Apoptotic Response to Anticancer AgentsBax在抗癌药物的凋亡反应的作用.pptVIP

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Role of BAX inthe Apoptotic Response to Anticancer AgentsBax在抗癌药物的凋亡反应的作用.ppt

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Role of BAX inthe Apoptotic Response to Anticancer AgentsBax在抗癌药物的凋亡反应的作用

Role of BAX in the Apoptotic Response to Anticancer Agents Zhang L, Yu J, Park BH, Kinzler KW, Vogelstein B. 2000. Role of BAX in the apoptotic response to anticancer agents. Science. 290(5493):989. Presented By: Trina Geiss Purpose The role of BAX in drug-induced apoptosis in human colorectal cancer cells. Generate cells that lack functional BAX genes. Find implications for cancer chemoprevention strategies. Terms Apoptosis=Programmed Cell Death BAX: Pro-Apoptotic Gene P53: Regulator of BAX, tumor suppressor gene. Bcl-2: Apoptosis Inhibiting Protein, silences effect of p53. MMR: (mismatch repair)Excise incorrect nucleotides. Chemotherapeutic agents: 5-flourouracil(5-FU) sulindac Background BAX is expressed in normal tissue Becomes inactive in the presence of certain cancers. This causes proliferation of cancer cells. Lower BAX activity means poor response to chemotherapy, fast tumor progression, and shorter survival. Role of p53 Drugs may induce BAX expression through p53-dependent transcription. BAX plays no role in murine p53 gene. Murine BAX has no p53-binding site in its promotor region. BAX deficiency in mice may promote apoptosis. Role of Bcl-2 Intimately involved in apoptosis. Role is confusing in drug-induced death. Interaction between BAX and Bcl-2 may cause cell death. Bcl-2, BAX, and p53 analysis could be good prognostic marker for patients who have already had surgery. Chemotherapeutic Agents 5-FU is the mainstay of treatment for colorectal cancer. Antimetabolite that induces cell death in a p53-dependent manner. Sulindac is the usual chemopreventive agent for those with colorectal cancer predisposition. It is a NSAID and it binds to and inhibits cellular proteins necessary for cell cycling. Overview Target of chemotherapeutic agents=human epithelial cells Clarify role of BAX Create colorectal cancer cells that differ only in presence of BAX gene. Obtaining the Cells Exploit MMR-deficient cells to mutate mononucleotide tracts. BAX has un